Despite extensive research in experimental animals over the past 6 years, the mechanism(s) of the cardiovascular, and renal effects of atrial natriuretic factor (ANF) remain unclear. The few human studies have provided limited insight into these mechanisms because various ANF analogues have been employed in pathophysiologic doses, and in most cases only minimal cardiovascular monitoring has been employed. Another major limitation of previous studies has been the lack of control of cardiac filling pressures during ANF infusions: central venous pressure and pulmonary capillary wedge pressure decline significantly during infusions. This results in an unphysiologic situation, i.e. high circulating levels of ANF during reduced atrial (and ventricular) stretch (which activates cardiac neural reflexes). An important and unique aspect of the proposed studies in man will be the maintenance of cardiac filling pressures during ANF infusions. Thus, it will be possible to implicate ANF as the sole mediator of the cardiovascular, renal, and hormonal responses provoked by its infusion. In these series of studies, invasive monitoring will be employed which will include: 1) placement of pulmonary artery catheters (to monitor left atrial filling pressure and to determine cardiac output) and 2) direct recordings of muscle sympathetic postganglionic nerve traffic by microneurography in volunteers. We will also examine potential mechanisms for the immediate and profound reductions in cardiac filling pressures produced by ANF infusions, by determining forearm venous distensibility and capillary permeability during infusions. Finally, we will examine important interactions of ANF with arterial and cardiopulmonary baroreflexes. Information from these series of studies will characterize the response to physiologic elevations of plasma ANF in humans and will provide much insight into the mechanisms of these effects. This basic information will be essential knowledge for understanding ANF's role in human pathophysiologic states associated with increased plasma concentrations of this hormone.